Primary progressive aphasia (PPA) is a gradual decline in language skills that results from neurodegenerative disease affecting language cortex. The typical patterns of spoken and written language impairments in individuals with PPA have been characterized in the literature (Gorno-Tempini et al., 2004;Hodges et al., 1992;Neary et al., 1998);however, the neural and cognitive bases for deficits in specific language domains are an area that warrants further investigation. In addition, individuals with PPA are currently under-referred and underserved by clinical professionals, including speech-language pathologists. In fact, the utility of behavioral treatment for the language impairments observed in PPA has yet to be systematically explored. The long-term goals of this three-year project are to characterize the cognitive and neuro anatomical bases for language decline in individuals with PPA and also to examine the utility of language treatment in each of the PPA variants. Specifically, the project aims to explore the relation between gray and white matter abnormalities and impairment to critical language domains in PPA;to assess the utility of theoretically motivated behavioral treatment for lexical retrieval in individuals with the disorder;and to examine anatomical and behavioral predictors of response to language treatment. In order to accomplish these aims, 30 individuals with PPA and 30 normal controls will be administered a comprehensive language battery comprising tests in the domains of syntax, semantics, phonology, and orthography. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) will be used to evaluate regional gray matter atrophy and white matter tract integrity and these imaging measures will be correlated with composite language measures. In addition, five individuals in each diagnostic variant of PPA will be administered a unique treatment protocol designed to capitalize on spared cognitive processes while attempting to remediate and/or compensate for impaired processes. Response to behavioral treatment in each PPA variant will be characterized by examining performance on trained and untrained items and tasks and by assessing maintenance following completion of structured treatment. Finally, pre-treatment measures of gray and white matter integrity as well as patterns of performance on composite language measures will be examined relative to response to treatment. These analyses will provide important evidence regarding the relation between neuro anatomical damage in PPA patients and their language characteristics and ability to respond to behavioral treatment. PUBLIC HEALTH RELEVANCE: This project's relevance to public health stems from its capacity to provide critical information regarding the nature and treatment of primary progressive aphasia, with the potential to enhance clinical management and rehabilitation of individuals with this debilitating disorder.